The goals of this project are to determine by fluorescent in situ hybridization (FISH) the pairing behavior and the level of gametic aneuploidy of specific chromosomes in human female germ cells from fetal life to the menopausal period. This data, collected over the entire germ cell developmental period, will be used to establish normative data for chromosomal anomalies in oocytes throughout reproductive life and has the potential to distinguish among the various hypotheses that have been proposed to explain the high incidence of aneuploidy in female gametes and the related maternal age effect. The operation of reduced recombination in disomic 21 gametes should be reflected in unpaired chromosome 21 homologues in post pachytene gametes. If maternal age is involved in the recombination effect, the level of unpaired chromosome 21's should increase with oocyte age. The level of aneuploidy at different ages could distinguish among the models of selection that have been proposed to explain maternal age dependent trisomy. If oogonial nondisjunction followed by selection of euploid gametes in early reproduction plays a significant role in trisomy 21, then a detectable level of gametic aneuploidy should be seen in oocytes from older women. Multicolor FISH analysis will permit the detection of heterologous associations in early meiosis which could be indicative of the hypothesized "searching" or "trial and error" process preceding pairing. It will allow determination of possible heterologous associations between acrocentrics which are known to form Robertsonian translocations. Identification of individual chromosomes in mammalian oogonial meiosis is normally not possible. This proposal represents the first time in which molecular technique will permit the general identification of chromosome and their possible interaction in mammalian oogenesis. Aneuploidy and pairing anomalies on fetal and adult oocytes will be identified using FISH with whole chromosome probes (chromosome painting). Fetal specimens will be obtained from second trimester terminations and from all stillborns undergoing autopsy. Adult oocytes will be extracted from surgical ovarian specimens from women of all ages who are undergoing indicated gynecologic surgery. Dual color FISH will be used to evaluate for heterologous associations between acrocentrics to analyze pairing relationships and their possible role in the formation of Robertsonian translocations. Multicolor FISH will be used to evaluate for heterologous associations in early meiosis to determine their significance in the formation of structural rearrangements.